CA2329659A1 - Perfluorinated esters of alkanoyl l-carnitine for the preparation of cationic lipids for the intracellular delivery of pharmacologically active compounds - Google Patents

Perfluorinated esters of alkanoyl l-carnitine for the preparation of cationic lipids for the intracellular delivery of pharmacologically active compounds Download PDF

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Publication number
CA2329659A1
CA2329659A1 CA002329659A CA2329659A CA2329659A1 CA 2329659 A1 CA2329659 A1 CA 2329659A1 CA 002329659 A CA002329659 A CA 002329659A CA 2329659 A CA2329659 A CA 2329659A CA 2329659 A1 CA2329659 A1 CA 2329659A1
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CA
Canada
Prior art keywords
acid
ester
carnitine
alkanoyl
perfluorinated
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CA002329659A
Other languages
French (fr)
Other versions
CA2329659C (en
Inventor
Mose Santaniello
Lucia Critelli
Nazareno Scafetta
Maria Grazia Cima
Maria Ornella Tinti
Claudio Pisano
Andrea Pucci
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sigma Tau Industrie Farmaceutiche Riunite SpA
Original Assignee
Sigma-Tau Industrie Farmaceutiche Riunite S.P.A.
Mose Santaniello
Lucia Critelli
Nazareno Scafetta
Maria Grazia Cima
Maria Ornella Tinti
Claudio Pisano
Andrea Pucci
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sigma-Tau Industrie Farmaceutiche Riunite S.P.A., Mose Santaniello, Lucia Critelli, Nazareno Scafetta, Maria Grazia Cima, Maria Ornella Tinti, Claudio Pisano, Andrea Pucci filed Critical Sigma-Tau Industrie Farmaceutiche Riunite S.P.A.
Publication of CA2329659A1 publication Critical patent/CA2329659A1/en
Application granted granted Critical
Publication of CA2329659C publication Critical patent/CA2329659C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Liposomes
    • A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers
    • A61K9/1272—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers with substantial amounts of non-phosphatidyl, i.e. non-acylglycerophosphate, surfactants as bilayer-forming substances, e.g. cationic lipids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C229/22—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated the carbon skeleton being further substituted by oxygen atoms

Abstract

Perfluorinated esters of alkanoyl L-carnitine of formula (I) are described, said esters are useful as cationic lipids for the intracellular delivery of pharmacologically active compounds.

Claims (19)

1. Perfluorinated ester of alkanoyl-L-carnitine with formula (I):
where:
R1 is alkanoyl, linear or branched, with 2-20 carbon atoms, optionally perfluorinated R2 is perfluorinated alkyl, linear or branched, with 4-20 carbon atoms; and X- is the anion of a pharmacologically acceptable acid.
2. Ester according to claim 1 in which R1 is selected from the group consisting of acetyl, propionyl, butyryl, valeryl, isova-leryl, undecanoyl, lauroyl, tridecafluoroheptanoyl, heptadecafluorononanoyl, heptacosafluoromyristoyl, pentadecafluoro-octanoyl and 5H-octafluoropentanoyl.
3. Ester according to claims 1 or 2 in which R2 is selected from the group consisting of: 1,1H-2,2H-tridecafluoro-octyl;
1,1H-2,2H-3,3H-pentafluoropentyl; 1,1H-2,2H-nonafluorohexyl;
1,1H-2,2H-3,3H-4,4H-5,5H-6,6H-nonafluorodecyl; 1,1H-2,2H-heptadecafluorodecyl; 1,1H-2,2H-heinicosafluorododecyl; and 1,1H-tricosafluorododecyl.
4. Ester according to claim 1, in which R1 has 4-12 carbon atoms and R2 has 5-12 carbon atoms.
5. Ester according to claims 1 or 2 in which X- is selected from the group consisting of: chloride: bromide; iodide; aspartate; acid aspartate; citrate; acid citrate; tartrate; mucate; phosphate; acid phosphate; fumarate; acid fumarate; glycerophosphate; glucose phosphate; lactate; maleate; acid maleate; orotate; oxalate; acid oxalate; sulphate; acid sulphate; trichloroacetate;
trifluoroacetate and methane sulphonate.
6. Undecanoyl-L-carnitine chloride 1,1H-2,2H-heptadecafluorodecyl ester.
7. Lauroyl-L-carnitine chloride 1,1H-2,2H-tridecafluoro-octyl ester.
8. Lauroyl-L-carnitine chloride 1,1H-2,2H-3,3H-pentafluoropentyl ester.
9. Undecanoyl-L-carnitine chloride 1,1H-2,2H-nonafluorohexyl ester.
10. Isovaleryl-L-carnitine chloride 1,1H-2,2H-3,3H-4,4H-5,5H-6,6H
nonafluoro-decyl ester.
11. Undecanoyl-L-carnitine chloride 1,1H-2,2H-3,3H-4,4H-5,5H-6,6H
nonafluoro-decyl ester.
12. Use of an ester according to anyone of claims 1-11 for the production of liposomes.
13. Liposome containing a perfluorinated ester of alkanoyl L-carnitine with formula (I):
where:
R1 is alkanoyl, linear or branched, with 2-20 carbon atoms, optionally perfluorinated R2 is perfluorinated alkyl, linear or branched, with 4-20 carbon atoms; and X- is the anion of a pharmacologically acceptable acid.
14. Liposome according to claim 13 in which R1 is selected from the group consisting of acetyl, propionyl, butyryl, valeryl, isovaleryl, undecanoyl, lauroyl, tridecafluoroheptanoyl, heptadecafluorononanoyl, heptacosafluoromyristoyl, pentadecafluoro-octanoyl and 5H-octafluoropentanoyl, R2 is selected from the group consisting of: 1,1H-2,2H-tridecafluoro-octyl;
1,1H-2,2H-3,3H-pentafluoropentyl; 1,1H-2,2H-nonafluorohexyl;
1,1H-2,2H-3,3H-4,4H-5,5H-6,6H-nonafluorodecyl;
1,1H-2,2H-heptadecafluorodecyl; 1,1H-2,2H-heinicosa-fluorododecyl; and 1,1H-tricosafluorododecyl, and X- is selected from the group consisting of: chloride: bromide; iodide; aspartate; acid aspartate; citrate; acid citrate; tartrate; mucate; phosphate; acid phosphate; fumarate; acid fumarate; glycerophosphate; glucose phosphate; lactate; maleate; acid maleate; orotate; oxalate; acid oxalate; sulphate; acid sulphate; trichloroacetate;
trifluoroacetate and methane sulphonate.
15. Use of a cationic liposome of claim 13 or 14 for the preparation of a medicament useful for the intracellular delivery of a pharmacologically active compound.
16. Use of a cationic liposome of claim 13 or 14 for the preparation of a medicament useful for promoting the interaction of a pharmacologically active compound with cell membrane receptors.
17. Use according to claim 15, wherein said pharmacologically active compound is a gene, optionally comprised in a suitable vector.
18. Use according to claim 15, wherein said medicament is useful for gene therapy.
19. Use according to claim 17 or 18, wherein said gene is .beta.-gal.
CA2329659A 1998-05-06 1999-05-04 Perfluorinated esters of alkanoyl l-carnitine for the preparation of cationic lipids for the intracellular delivery of pharmacologically active compounds Expired - Fee Related CA2329659C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
ITRM98A000293 1998-05-06
IT98RM000293A IT1299172B1 (en) 1998-05-06 1998-05-06 PERFLUORINATED ESTERS OF ALCANOYL L-CARNITINE USABLE AS CATIONIC LIPIDS FOR THE INTRACELLULAR DELIVERY OF COMPOUNDS
PCT/IT1999/000117 WO1999057094A2 (en) 1998-05-06 1999-05-04 Perfluorinated esters of alkanoyl l-carnitine for the preparation of cationic lipids for the intracellular delivery of pharmacologically active compounds

Publications (2)

Publication Number Publication Date
CA2329659A1 true CA2329659A1 (en) 1999-11-11
CA2329659C CA2329659C (en) 2010-07-20

Family

ID=11405901

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2329659A Expired - Fee Related CA2329659C (en) 1998-05-06 1999-05-04 Perfluorinated esters of alkanoyl l-carnitine for the preparation of cationic lipids for the intracellular delivery of pharmacologically active compounds

Country Status (13)

Country Link
US (1) US6476243B1 (en)
EP (1) EP1075461B1 (en)
JP (1) JP4366014B2 (en)
KR (1) KR100573008B1 (en)
AT (1) ATE272047T1 (en)
AU (1) AU3846599A (en)
CA (1) CA2329659C (en)
DE (1) DE69918974T2 (en)
DK (1) DK1075461T3 (en)
ES (1) ES2226384T3 (en)
IT (1) IT1299172B1 (en)
PT (1) PT1075461E (en)
WO (1) WO1999057094A2 (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT1306129B1 (en) 1999-04-13 2001-05-30 Sigma Tau Ind Farmaceuti ESTERS OF L-CARNITINE OR ALCANOYL L-CARNITINE USABLE CATIONIC COMELIPIDS FOR INTRACELLULAR PLACING OF COMPOUNDS
IT1316990B1 (en) * 2000-02-17 2003-05-26 Sigma Tau Ind Farmaceuti METHOD TO INCREASE GENE EXPRESSION FOR TRANSFECTED GENES.

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT1116037B (en) * 1979-04-23 1986-02-10 Sigma Tau Ind Farmaceuti ACIL CARNITINE ESTERS AND AMIDS THEIR PREPARATION PROCEDURES AND THERAPEUTIC USE
IT1258370B (en) * 1992-03-02 1996-02-26 Sigma Tau Ind Farmaceuti ESTERS OF L-CARNITINE AND ACIL L-CARNITINE EQUIPPED WITH SELECTIVE MYO-RELAXING ACTIVITY ON THE GASTRO-INTESTINAL APPARATUS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM.
US5846516A (en) * 1992-06-03 1998-12-08 Alliance Pharmaceutial Corp. Perfluoroalkylated amphiphilic phosphorus compounds: preparation and biomedical applications
FR2694195B1 (en) * 1992-07-30 1994-09-23 Sederma Sa New slimming cosmetic compositions.

Also Published As

Publication number Publication date
DK1075461T3 (en) 2004-12-06
KR20010043234A (en) 2001-05-25
US6476243B1 (en) 2002-11-05
JP4366014B2 (en) 2009-11-18
CA2329659C (en) 2010-07-20
ITRM980293A0 (en) 1998-05-06
JP2002513779A (en) 2002-05-14
EP1075461B1 (en) 2004-07-28
ATE272047T1 (en) 2004-08-15
WO1999057094A2 (en) 1999-11-11
IT1299172B1 (en) 2000-02-29
DE69918974D1 (en) 2004-09-02
DE69918974T2 (en) 2005-08-11
PT1075461E (en) 2004-11-30
ES2226384T3 (en) 2005-03-16
EP1075461A2 (en) 2001-02-14
ITRM980293A1 (en) 1999-11-06
WO1999057094A3 (en) 2000-01-27
KR100573008B1 (en) 2006-04-24
AU3846599A (en) 1999-11-23

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